Specification and Evaluation of Plasticizer Migration Simulants for Human Blood Products: A Delphi Study.

Potentially toxic plasticizers are commonly added to polyvinyl chloride medical devices for transfusion in order to improve their flexibility and workability. As the plasticizers are not chemically bonded to the PVC, they can be released into labile blood products (LBPs) during storage. Ideally, LBPs would be used in laboratory studies of plasticizer migration from the medical device. However, short supply (i.e., limited stocks of human blood in collection centres) has prompted the development of specific simulants for each type of LBP in the evaluation of new transfusion devices. We performed a Delphi study with a multidisciplinary panel of 24 experts. In the first (qualitative) phase, the panel developed consensus definitions of the specification criteria to be met by each migration simulant. Next, we reviewed the literature on techniques for simulating the migration of plasticizers into LBPs. A questionnaire was elaborated and sent out to the experts, and the replies were synthesized in order to obtain a consensus. The qualitative study established specifications for each biological matrix (whole blood, red blood cell concentrate, plasma, and platelet concentrate) and defined the criteria required for a suitable LBP simulant. Ten criteria were suggested: physical and chemical characteristics, opacity, form, stability, composition, ability to mimic a particular clinical situation, ease and safety of use, a simulant-plastic interaction correlated with blood, and compatibility with analytical methods. The questionnaire data revealed a consensus on the use of natural products (such as pig's blood) to mimic the four LBPs. Opinions diverged with regard to synthetic products. However, an isotonic solution and a rheological property modifier were considered to be of value in the design of synthetic simulants. Consensus reached by the Delphi group could be used as a database for the development of simulants used to assess the migration of plasticizers from PVC bags into LBPs.

Surface modification of polypropylene nonwovens with LDV peptidomimetics and their application in the leukodepletion of blood products.

For clinical indications and according to European standards, a depletion of the leukocytes from whole blood has to be realized before transfusion to a patient. In this study, the surface of a layer of meltblown oxygen-plasma treated polypropylene nonwoven (O(2)-PP), making part of the composition of leukodepletion filters, was modified with bioactive molecules to enhance the adhesion of leukocytes. These synthetic small molecules (called peptidomimetics) mimic the "Leu-Asp-Val" (LDV) tripeptide sequence recognized by the α(4)ß(1) integrin, a receptor expressed on leukocytes. Their activity, as ligands of the α(4)ß(1) integrin, was confirmed through cell adhesion assays. The peptidomimetics were covalently immobilized on O(2)-PP nonwoven via activation of the hydroxyl- and carboxyl-functions displayed on the polymer surface with trifluoro-triazine reagent, or were simply deposited on the O(2)-PP surface. The treated materials were characterized by X-ray photoelectron spectroscopy, wettability, and morphological analyses, before and after steam sterilization. Experimental filters composed of 10 layers of O(2)-PP nonwovens and a last layer modified with the peptidomimetics were evaluated, using whole blood filtration assays, for their leukodepletion efficiency, the recovery of red cells and platelets and the waste of blood, with an objective to design new filters fulfilling practical and medical criteria.